BR112020022790A2 - novo composto que exibe atividade inibitória de enteropeptidase - Google Patents
novo composto que exibe atividade inibitória de enteropeptidase Download PDFInfo
- Publication number
- BR112020022790A2 BR112020022790A2 BR112020022790-0A BR112020022790A BR112020022790A2 BR 112020022790 A2 BR112020022790 A2 BR 112020022790A2 BR 112020022790 A BR112020022790 A BR 112020022790A BR 112020022790 A2 BR112020022790 A2 BR 112020022790A2
- Authority
- BR
- Brazil
- Prior art keywords
- carbamimidoyl
- thiazol
- carboxylate
- amino
- carbonyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 225
- 108010013369 Enteropeptidase Proteins 0.000 title claims abstract description 34
- 102100029727 Enteropeptidase Human genes 0.000 title claims abstract description 34
- 230000002401 inhibitory effect Effects 0.000 title abstract description 26
- 150000003839 salts Chemical class 0.000 claims abstract description 39
- 208000008589 Obesity Diseases 0.000 claims abstract description 18
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- 208000030159 metabolic disease Diseases 0.000 claims abstract description 14
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 13
- 238000011282 treatment Methods 0.000 claims abstract description 13
- 208000031226 Hyperlipidaemia Diseases 0.000 claims abstract description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
- 230000002265 prevention Effects 0.000 claims abstract description 8
- -1 (4-carbamimidoyl-2-fluorophenoxy) carbonyl Chemical group 0.000 claims description 389
- 238000002360 preparation method Methods 0.000 claims description 104
- 239000000126 substance Substances 0.000 claims description 58
- 239000002253 acid Substances 0.000 claims description 56
- 229910052757 nitrogen Inorganic materials 0.000 claims description 49
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical group NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 32
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 27
- 125000005605 benzo group Chemical group 0.000 claims description 24
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 23
- 230000003287 optical effect Effects 0.000 claims description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
- 229910052799 carbon Inorganic materials 0.000 claims description 17
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 17
- 125000005843 halogen group Chemical group 0.000 claims description 17
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Chemical group CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 16
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- 150000001408 amides Chemical group 0.000 claims description 16
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- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Chemical group CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 16
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 16
- DMPZJACLHDWUFS-UHFFFAOYSA-N 1,3-benzothiazole-6-carboxylic acid Chemical compound OC(=O)C1=CC=C2N=CSC2=C1 DMPZJACLHDWUFS-UHFFFAOYSA-N 0.000 claims description 14
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- 210000000496 pancreas Anatomy 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 210000005259 peripheral blood Anatomy 0.000 description 1
- 239000011886 peripheral blood Substances 0.000 description 1
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- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 230000000291 postprandial effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 201000009104 prediabetes syndrome Diseases 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 229940107700 pyruvic acid Drugs 0.000 description 1
- 229940103440 qsymia Drugs 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 208000001076 sarcopenia Diseases 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- GLUDYSUVZMFKLB-UHFFFAOYSA-N tert-butyl 1,3-thiazole-5-carboxylate Chemical compound CC(C)(C)OC(=O)C1=CN=CS1 GLUDYSUVZMFKLB-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229940002552 xenical Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/426—1,3-Thiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/428—Thiazoles condensed with carbocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/42—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D277/82—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR10-2018-0053316 | 2018-05-09 | ||
| KR10-2018-0053315 | 2018-05-09 | ||
| KR20180053315 | 2018-05-09 | ||
| KR20180053316 | 2018-05-09 | ||
| PCT/KR2019/005997 WO2019216742A1 (ko) | 2018-05-09 | 2019-05-08 | 엔테로펩디아제 억제 활성을 나타내는 신규 화합물 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| BR112020022790A2 true BR112020022790A2 (pt) | 2021-02-02 |
Family
ID=68468129
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| BR112020022790-0A BR112020022790A2 (pt) | 2018-05-09 | 2019-05-08 | novo composto que exibe atividade inibitória de enteropeptidase |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US11447480B2 (ja) |
| EP (1) | EP3778577B1 (ja) |
| JP (1) | JP7199774B2 (ja) |
| KR (1) | KR102325422B1 (ja) |
| CN (1) | CN112105604B (ja) |
| AU (1) | AU2019265268C1 (ja) |
| BR (1) | BR112020022790A2 (ja) |
| CA (1) | CA3099268C (ja) |
| CL (1) | CL2020002887A1 (ja) |
| CO (1) | CO2020014186A2 (ja) |
| DK (1) | DK3778577T3 (ja) |
| IL (1) | IL278435B1 (ja) |
| JO (1) | JOP20200282A1 (ja) |
| MX (1) | MX2020011960A (ja) |
| PE (1) | PE20211496A1 (ja) |
| PH (1) | PH12020551900A1 (ja) |
| RU (1) | RU2768755C1 (ja) |
| SG (1) | SG11202011083PA (ja) |
| UA (1) | UA126099C2 (ja) |
| WO (1) | WO2019216742A1 (ja) |
| ZA (1) | ZA202007260B (ja) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE9201956D0 (sv) | 1992-06-25 | 1992-06-25 | Kabi Pharmacia Ab | Novel nicotinicacid esters |
| DE10228132A1 (de) | 2002-06-24 | 2004-01-22 | Arzneimittelwerk Dresden Gmbh | Amide cyclischer Aminosäuren als PDE 4 Inhibitoren |
| CA2514573A1 (en) | 2003-01-27 | 2004-08-12 | Astellas Pharma Inc. | Thiazole derivatives and their use as vap-1 inhibitors |
| DE602004028907D1 (de) * | 2003-02-06 | 2010-10-14 | Bristol Myers Squibb Co | Als kinaseinhibitoren geeignete verbindungen auf thiazolylbasis |
| US7335658B2 (en) | 2003-07-30 | 2008-02-26 | Xenon Pharmaceuticals Inc. | Pyridazine derivatives and their use as therapeutic agents |
| BRPI0607307A2 (pt) * | 2005-01-26 | 2009-08-25 | Irm Llc | compostos e composições como inibidores de proteìna cinase |
| WO2008124393A1 (en) | 2007-04-04 | 2008-10-16 | Irm Llc | Benzothiazole derivatives and their use as protein kinase inhibitors |
| CA2703106C (en) * | 2007-10-24 | 2015-12-01 | Astellas Pharma Inc. | Azolecarboxamide derivatives as trka inhibitors |
| EP2314587A4 (en) | 2008-07-17 | 2012-01-25 | Asahi Kasei Pharma Corp | HETEROCYCLIC NITROGEN COMPOUND |
| CN102822154B (zh) * | 2009-12-07 | 2016-06-01 | 味之素株式会社 | 杂芳基羧酸酯衍生物 |
| EP2725016B1 (en) | 2011-06-07 | 2016-12-21 | EA Pharma Co., Ltd. | Heterocyclic carboxylic acid ester derivative |
| US9346776B2 (en) * | 2014-02-13 | 2016-05-24 | Takeda Pharmaceutical Company Limited | Fused heterocyclic compound |
| US9428470B2 (en) | 2014-02-13 | 2016-08-30 | Takeda Pharmaceutical Company Limited | Heterocyclic compound |
| WO2016104630A1 (ja) | 2014-12-26 | 2016-06-30 | 武田薬品工業株式会社 | 縮合複素環化合物 |
| WO2016158788A1 (ja) | 2015-03-27 | 2016-10-06 | 武田薬品工業株式会社 | 縮合複素環化合物 |
| EP3523292B1 (en) | 2016-10-10 | 2021-12-15 | Dong-A Socio Holdings Co., Ltd. | Heteroaryl compounds and their use as mer inhibitors |
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2019
- 2019-05-08 AU AU2019265268A patent/AU2019265268C1/en active Active
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- 2019-05-08 WO PCT/KR2019/005997 patent/WO2019216742A1/ko unknown
- 2019-05-08 JP JP2020562707A patent/JP7199774B2/ja active Active
- 2019-05-08 CN CN201980031203.8A patent/CN112105604B/zh active Active
- 2019-05-08 EP EP19800582.9A patent/EP3778577B1/en active Active
- 2019-05-08 RU RU2020136431A patent/RU2768755C1/ru active
- 2019-05-08 CA CA3099268A patent/CA3099268C/en active Active
- 2019-05-08 JO JOP/2020/0282A patent/JOP20200282A1/ar unknown
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- 2019-05-08 IL IL278435A patent/IL278435B1/en unknown
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| IL278435B1 (en) | 2024-02-01 |
| CN112105604A (zh) | 2020-12-18 |
| ZA202007260B (en) | 2022-07-27 |
| JP7199774B2 (ja) | 2023-01-06 |
| CL2020002887A1 (es) | 2021-05-14 |
| KR102325422B1 (ko) | 2021-11-11 |
| MX2020011960A (es) | 2021-01-15 |
| AU2019265268C1 (en) | 2022-08-04 |
| KR20190129009A (ko) | 2019-11-19 |
| AU2019265268B2 (en) | 2022-04-28 |
| CN112105604B (zh) | 2024-01-09 |
| IL278435A (ja) | 2021-03-01 |
| CO2020014186A2 (es) | 2020-11-30 |
| UA126099C2 (uk) | 2022-08-10 |
| DK3778577T3 (da) | 2023-09-25 |
| US11447480B2 (en) | 2022-09-20 |
| JP2021521260A (ja) | 2021-08-26 |
| EP3778577A4 (en) | 2021-03-31 |
| AU2019265268A1 (en) | 2020-12-17 |
| WO2019216742A1 (ko) | 2019-11-14 |
| JOP20200282A1 (ar) | 2020-11-08 |
| US20210284634A1 (en) | 2021-09-16 |
| RU2768755C1 (ru) | 2022-03-24 |
| SG11202011083PA (en) | 2020-12-30 |
| EP3778577A1 (en) | 2021-02-17 |
| CA3099268A1 (en) | 2019-11-14 |
| PH12020551900A1 (en) | 2021-05-31 |
| PE20211496A1 (es) | 2021-08-11 |
| EP3778577B1 (en) | 2023-08-30 |
| CA3099268C (en) | 2023-03-07 |
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